This invention relates generally to the field of heterocyclic chemistry and the synthesis of nitrogen heterocycles, and more specifically to a novel process for the synthesis of derivatives of 4-amino-1,2,4-(4H)triazole from hydrazine and carboxylic acids.
Derivatives of 4-amino-1,2,4-(4H)triazole have well-known utility as intermediates in the synthesis of a large number of 1,2,4-triazole compounds that are utilized as herbicides (e.g., German Patent Nos. 2,653,447 and 2,822,014), plant growth regulators (e.g., German Patent No. 2,737,489 and British Patent No. 2,050,334), and as fungicides (e.g., Chem. Abstr., 104, 124849 (1986); Valcke et al. Proc.-Annu. Meet. Am. Wood-Preserv. Assoc. 1985, 81, 196. also Jager, Pestic. Chem. Hum. Welfare Environ., Proc. Int. Congr. Pestic. Chem., 5th, Vol. 1, pp. 55-65). In addition, 4-amino-1,2,4-(4H)triazole itself has well-known utility as a nitrification inhibitor (e.g., U.S. Pat. No. 3,697,244; Kucharski and Chodan, Zasz. Nauk, Akad. Roln-Tech. Olsztynie, Roln., 36, 109-116 (Chem. Abstr., 101, 129600 (1984)).
The synthesis of 1,2,4-triazole derivatives has been well-explored, and is generally reviewed in C. Temple, Jr., "Triazoles 1,2,4," The Chemistry of Heterocyclic Compounds, Vol. 37, John Wiley & Sons, Inc., New York, 1981. One process for the synthesis of 4-amino-1,2,4-(4H)triazole is described in Organic Syntheses (Vol. 24, p. 12, 1944) in which ethyl formate and 85% hydrazine hydrate are combined, then heated at progressively higher temperatures, first distilling ethanol and then water out of the reaction mixture, and then heating the remaining residue up to 200.degree. C. the residue, while still hot, is treated with solvents, and after extensive manipulation crystallized 4-amino-1,2,4-(4H)triazole is reportedly obtained in a 65%-71% yield. This process is undesirable because it requires the use of flammable and volatile ethyl formate, it requires close temperature control and high temperatures, and it reportedly produces the product in only moderate yield. Furthermore, the 4-amino-1,2,4-(4H)triazole is of low purity, requiring the use of decolorizing carbon. The recovered wet ethanol by-produce is of little or no value unless further costly procedures are used to purify it.
Herbst and Garrison (J. Org. Chem., 18, 872 (1953)) disclosed the preparation of a series of 3,5-dialkyl-1,2,4-(4H)triazoles by an uncatalyzed process requiring the heating of hydrazine hydrate with carboxylic acids while removing water by distillation. The process requires excessively high temperatures of 200.degree. to 280.degree. C., and the yields of some substituted products utilizing this process are unacceptably low and poorly reproducible.
Mizushima et al. (Japan Patent No. 71 35,056 (1971); Chem. Abstr., 76, 3867 (1972)) disclosed the reaction of formic acid with hydrazine hydrate and phosphoric acid at 160.degree.-180.degree. C. to give 96.6% yield of 4-amino-1,2,4-(4H)triazole. However, the product of this process if also of extremely low purity because phosphoric acid remains in the product, rendering it unsuitably inpure for most uses.
More recently, Jaromir and Jaromir [Czech. Patent 216,554, (1984); Chem. Abst., 103, 160520 (1985)] disclosed the reaction of formamide and hydrazine in the presence of a strongly acid ion exchange resin catalyst, first using heat and vacuum to remove ammonia and water produced during the reaction, and then heating to 220.degree. C., preferably to 160.degree.-180.degree. C., which are uncomfortably high temperatures, for a period of time to complete the reaction. The ion exchange resin is reportedly removed from crude product at an elevated temperature of 100.degree. C., and 4-amino-1,2,4-(4H)triazole is crystallized from the melt in 80%-85% yield, leaving unreacted formamide that must be recovered and recycled. This process also suffers from the disadvantages of producing a by-product of unsubstituted 1,2,4-triazole, which results in an impurity in the desired 4-amino-1,2,4-(4H)triazole, as well as a lower yield of 4-amino-1,2,4-(4H)triazole.
Applicants' discovery overcomes these inadequacies in the existing art, and results in the synthesis reaction proceeding at attractively lower temperatures much more suitable for commercial manufacturing operations, with no significant by-products, resulting both in easier product separation and in high yields and purity particularly in the case of 4-amino-1,2,4-(4H)triazole.